Our overall objective over the past 10 years has been to relate herpes simplex viruses (HSV) to cervical cancer and more recently to other human cancers, to obtain evidence for causality, and to define basic virus-cell and virus-host interactions with HSV infection. We have recently developed a rapid assay (the anti-complement immunofluorescence (ACIF) test for detecting HSV antigens directly in human cervical cancers. The proposed studies are: (1) to test a variety of human cancers for the presence of HSV-1 or HSV-2 antigens by the ACIF test; (2) to determine and define the specific proteins associated with this reaction and to attempt a correlation with the "early" on "non-virion" HSV antigens found by other workers; (3) to develop serological assays for the detection of antibodies to specific HSV or tumor antigens in the serum of patients with various types of cancer. These studies, although still unlikely to prove causality conclusively, should provide: (a) a further strong link between herpes simplex viruses and human cancers; (b) potentially useful and simple assays for diagnosis and prognosis of certain cancers; (c) improved information of herpesvirus-cell interactions. In addition, similar approaches might be employed with other viruses potentially oncogenic in humans.